Subcutaneous on par with intravenous pembrolizumab for metastatic NSCLC

Pembrolizumab administered subcutaneously (SC) is noninferior to the intravenous (IV) strategy in terms of overall exposure and trough concentrations, with similar efficacy and consistent safety profiles in patients with treatment-naive metastatic nonsmall cell lung cancer (NSCLC), reports a study.

In addition, “the immunogenicity of pembrolizumab SC was low, and local injection-site adverse events (AEs) were infrequent, mild, and nonserious,” the researchers said.

A total of 377 participants with newly diagnosed stage IV or nonsquamous NSCLC without sensitizing GFR, ALK, or ROS1 alterations were randomized to pembrolizumab SC (n=251) 790 mg every 6 weeks (Q6W) or IV (n=126) 400 mg Q6W (18 cycles), with platinum-doublet chemotherapy.

The median time from randomization to data cutoff was 9.6 months, and the median injection time for pembrolizumab SC was 2.0 min.

The primary endpoints were pharmacokinetic exposure measures of cycle 1 area under the curve (AUC_{0-6 weeks}) and steady-state trough concentration (C_trough) of pembrolizumab, with a noninferiority margin of 0.8. Other endpoints included additional pharmacokinetic exposure measures, pembrolizumab immunogenicity, efficacy, and safety.

The geometric mean ratio (GMR) for cycle 1 AUC_{0-6 weeks} was 1.14 (96 percent confidence interval [CI], 1.06–1.22; p<0.0001), while that for steady-state C_trough was 1.67 (94 percent CI, 1.52–1.84; p<0.0001). Other endpoints were within the established bounds for pembrolizumab. [Ann Oncol 2025;36:775-785]

Antipembrolizumab antibodies were found in 1.4 percent of patients in the SC arm and 0.9 percent in the IV arm. Additionally, the objective response rate (ORR) was higher in the SC than the IV arm (45.4 percent vs 42.1 percent; ORR ratio, 1.08, 95 percent CI, 0.85–1.37). Other efficacy measures were comparable, and safety profiles were consistent between groups. 

“These results demonstrate that pembrolizumab SC is a treatment option for all indications where pembrolizumab IV can be used, with the potential to improve the patient experience and reduce time demands in the clinic, which may streamline treatment centre workflows and reduce healthcare resource utilization,” the researchers said.

Survival

Results for ORR, median progression-free survival (PFS), and median duration of response for the two treatment arms were consistent with those seen in the KEYNOTE trials of pembrolizumab IV plus chemotherapy for metastatic NSCLC. [N Engl J Med 2018;378:2078-2092; N Engl J Med 2018;379:2040-2051]

“As of this analysis, the median duration of follow-up in the study is shorter than those of the KEYNOTE-189 and KEYNOTE-407 studies,” the researchers said. “Therefore, the overall survival data are considered immature.” 

Results of the subgroup analysis were consistent for ORR and PFS across all groups. In addition, no new safety findings were pembrolizumab SC were observed, and local injection-site AE were rare and mild.

“SC administration of therapeutic agents has been shown to have advantages over IV administration, including higher patient satisfaction, lower emotional burden (eg, less anxiety and stress), and greater patient and provider preference,” the researchers said. [Adv Ther 2024;41:4396-4417; Eur J Cancer 2021;152:223-232; Ann Oncol 2017;28:836-842; Patient Prefer Adherence 2024;18:1857-1871] 

“Moreover, SC administration has been associated with improvements in administration workflows, including shorter clinic time, and provider time,” they added. [Lancet Oncol 2013;14:962-970]